Brand Names: U.S.

Trelstar Mixject

Trelstar [DSC]

Triptodur

Pharmacologic Category

Gonadotropin Releasing Hormone Agonist

Pharmacology

Triptorelin is an agonist analog of gonadotropin releasing hormone (GnRH) and causes suppression of ovarian and testicular steroidogenesis due to decreased levels of LH and FSH with subsequent decrease in testosterone (male) and estrogen (female) levels. After chronic and continuous administration, usually 2 to 4 weeks after initiation, a sustained decrease in LH and FSH secretion occurs. When used for ART, prevents premature LH surge in women undergoing controlled ovarian hyperstimulation.

Distribution

Vd: 30 to 33 L

Metabolism

Unknown; unlikely to involve CYP; no known metabolites

Excretion

Urine (42% as intact peptide); hepatic

Time to Peak

Trelstar: 1 to 3 hours; Triptodur: 4 hours

Half-Life Elimination

2.8 ± 1.2 hours

Moderate-to-severe renal impairment: 6.6 to 7.7 hours

Hepatic impairment: 7.6 hours

Protein Binding

None

Special Populations: Renal Function Impairment

There is a decrease in total Cl proportional to decrease in CrCl and increased Vd and half-life. Patients with renal impairment had 2- to 4-fold higher exposure (AUC) values than younger healthy men.

Special Populations: Hepatic Function Impairment

The decrease in triptorelin Cl is more pronounced. Triptorelin half-life increase is similar to renal impairment. Patients with hepatic impairment had 2- to 4-fold higher exposure (AUC) values than younger healthy men.

Special Populations: Elderly

Triptorelin clearance is partly correlated to total CrCl, which is well known to decrease with age.

Off Label Uses

Endometrial stromal sarcoma

Data from a limited number of case reports and clinical experience suggest triptorelin may be beneficial in the treatment of endometrial stromal sarcoma [Burke 2004], [Jin 2015]. Clinical experience also suggests the utility of gonadotropin-releasing hormone receptor analogs, including triptorelin may be of benefit in the treatment of endometrial stromal sarcoma [Amant 2009], [ESMO 2012]. Additional studies are necessary to further define the role of triptorelin in the management of this condition.

Additional Off-Label Uses

Contraindications

Known hypersensitivity to triptorelin or any component of the formulation, other GnRH agonists or GnRH; pregnancy

Canadian labeling: Additional contraindications (not in the US labeling): Breastfeeding women

Dosing: Adult

Prostate cancer (advanced): Trelstar: IM:

3.75 mg once every 4 weeks or

11.25 mg once every 12 weeks or

22.5 mg once every 24 weeks

Controlled ovarian hyperstimulation for assisted reproductive technologies (ART) (adjunctive therapy): Decapeptyl (Canadian product): Females: SubQ: Usual dose: 0.1 mg once daily initiated on day 2 or 3 or days 21 to 23 of menstrual cycle (or 5 to 7 days prior to expected onset of menses). Dose may be adjusted according to ovarian response as measured by ovarian ultrasound with or without serum estradiol levels. Treatment is continued until follicles achieve suitable size (typically 4 to 7 weeks).

Endometrial stromal sarcoma (off-label use): IM: 3.75 mg once every 28 days for ~3 to 5 months (Jin 2015). Additional studies are necessary to further define the role of triptorelin in the management of this condition.

Note: May cause an initial increase in androgen concentrations, which may be treated with an antiandrogen (eg, flutamide, cyproterone) for 1 to 2 months (Guay 2009). Avoid use in patients with osteoporosis or active pituitary pathology.

Administration

IM: Administer by IM injection into the buttock (Trelstar) or into the buttock or thigh (Triptodur); alternate injection sites. Administer immediately after reconstitution. Must administer under the supervision of a health care provider.

Decapeptyl [Canadian product] is administered by subcutaneous injection into the lower abdomen; alternate injection sites. If a dose is missed, it can be administered on the same day; however, do not double doses. Must administer under the supervision of a health care provider.

Storage

Trelstar: Store at 20°C to 25°C (68°F to 77°F). Do not freeze MIXJECT system. Administer immediately after reconstitution.

Triptodur: Store at 20°C to 25°C (68°F to 77°F). Do not freeze.

Decapeptyl [Canadian product]: Store at 2°C to 8°C (36°F to 46°F); do not freeze. Protect from light.

MiFEPRIStone: May enhance the QTc-prolonging effect of QTc-Prolonging Agents (Indeterminate Risk and Risk Modifying). Management: Though the drugs listed here have uncertain QT-prolonging effects, they all have some possible association with QT prolongation and should generally be avoided when possible. Consider therapy modification

QTc-Prolonging Agents (Highest Risk): QTc-Prolonging Agents (Indeterminate Risk and Risk Modifying) may enhance the QTc-prolonging effect of QTc-Prolonging Agents (Highest Risk). Management: Avoid such combinations when possible. Use should be accompanied by close monitoring for evidence of QT prolongation or other alterations of cardiac rhythm. Consider therapy modification

Warnings/Precautions

Concerns related to adverse effects:

• Cardiovascular effects: Androgen-deprivation therapy (ADT) may increase the risk for cardiovascular disease (Levine 2010). Myocardial infarction, sudden cardiac death and stroke have been reported in men receiving GnRH agonists. ADT may prolong the QT/QTc interval; consider the benefits of ADT versus the risk for QT prolongation in patients with a history of QTc prolongation, congenital long QT syndrome, heart failure, frequent electrolyte abnormalities, and in patients with medications known to prolong the QT interval. Consider periodic monitoring of electrocardiograms and electrolytes in at-risk patients.

• Hyperglycemia: Hyperglycemia and an increased risk of developing diabetes has been reported with therapy and may manifest as diabetes or worsening of glycemic control in patients with diabetes. Monitor blood glucose and/or glycosylated hemoglobin (HbA1c) as clinically necessary.

• Psychiatric effects: Symptoms of emotional lability (eg, crying, irritability, anger, aggression, impatience) have been reported with GnRH agonists, including triptorelin; monitor for the development or worsening of psychiatric symptoms.

• Seizures: Seizures have been reported with GnRH agonists, including triptorelin in patients with or without a history of seizures or other conditions or concurrent medications associated with seizures.

• Spinal cord compression: Cases of spinal cord compression, which may contribute to weakness or paralysis (possible fatal complications), have been reported; observe patients with metastatic vertebral lesions closely during the first few weeks of treatment.

• Symptom flare: Transient initial increases in gonadotropins and sex steroids leading to a worsening of symptoms may be observed during the first few weeks of therapy or after subsequent doses. Patients with prostate cancer may experience new or increased bone pain, neuropathy, hematuria, or urethral or bladder outlet obstruction. Female patients with central precocious puberty may experience transient vaginal bleeding.

Disease-related concerns:

• Urinary tract obstruction: Observe patients with urinary tract obstruction closely during the first few weeks of treatment.

Treatment of precocious puberty: Monitor response to therapy with LH levels after a GnRH or GnRH agonist stimulation test, basal LH, or serum sex steroid levels beginning 1 to 2 months after initiation of therapy, during therapy, and with each subsequent dose; height every 3 to 6 months; bone age (periodically)

Treatment of paraphilia/hypersexuality (off-label use): The following monitoring has been recommended for other GnRH agonists: CBC (baseline, monthly for 4 months then every 6 months); serum testosterone (baseline, monthly for 4 months then every 6 months); serum LH (baseline and every 6 months), FSH (baseline), serum BUN and creatinine (baseline and every 6 months); bone density (baseline and yearly); ECG (baseline) (Reilly 2000)

Pregnancy Risk Factor

X

Pregnancy Considerations

Use is contraindicated in pregnant women. When used for ART, pregnancy must be ruled out prior to therapy and nonhormonal contraception should be used until menses occurs. Due to the short half-life of triptorelin (formulations used for ART), it is not expected to be present in the maternal serum at the time of embryo transfer. In case reports, spontaneous abortion, congenital anomalies, and other adverse events have been reported following triptorelin (Decapeptyl [Canadian product]) exposure during pregnancy.

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.